Spindlin1 Overexpression Induces Metaphase Arrest And Mitotic Catastrophe

Spin/ssty gene family is high conserved and very abundant transcript involved in gametogenesis, which was known to play a critical role in cell cycle regulation during meiosis and early embryogenesis. Previously, we have identified human gene spindlin1 as a homologue of spin/ssty gene family from ovarian cancer cells and reported that ectopic expression of spindlin1 could increase the G2/M population,transform NIH3T3 cells and at last induce tumorigenesis in nude mouse. Moreover, we reported the crystal structure of human spindlin1, as consisted of three tandem repeats of Tudor-like domains and showed that spindlin1 possessed dsDNA binding activity and exhibited higher affinity for super helical dsDNA than for open cycle dsDNA. Nevertheless, our knowledge about the members of spin/ssty family in meiosis/mitosis is still fragmentary and the biological roles of spindlin1 in cell cycle and oncogenesis are still largely unknown. Here, our result showed that spindlin1, as a nuclear protein, is relocated during mitosis. Fractions of spindlin1 proteins were localized to the mitotic spindle from prometaphase to metaphase, and were enriched at midzone following anaphase entering. We also showed that ectopic expression of spindlin1 provoked aberrant mitosis, metaphase arrest, mitotic catastrophe, and genomic instability. Furthermore, we found that Mad2 up-regulation, interaction with Hsp70/Kid and activation of spindle checkpoint may contribute to these changes in spindlin1-overexpressed cells. Taken together, these data suggestted that spindin1 may be involved in concordance of chromosome movement, congression and segregation and ectopic expression of spindlin1 was detrimental for genetic stability and can potentially contribute to cancer development.